Project Summary/Abstract Cancer is the leading cause of morbidity and mortality in the US and in the world. One approach to reducing the risk and burden of cancer is to use preventive agents and interventions that are effective and safe. According to the Division of Cancer Prevention (DCP) at the National Cancer Institute (NCI), this requires the systematic development of cancer preventive agents and interventions, with three critical components; i) preclinical/toxicology studies for identification of agents, ii) early phase trials of identified agents and other promising interventions, and iii) late phase III trials of preventive agents and interventions that have successfully passed through early phase trials, in a three-legged approach. The goal of the Cancer Prevention Clinical Trials Network (CP-CTNet) is to identify safe and effective preventive agents and interventions in order to advance their further clinical development for cancer prevention. Further clinical development is to be undertaken in late phase III trials conducted by the third leg, i.e. the National Community Oncology Research Program (NCORP), supported by the DCP's Community Oncology and Prevention Trials Research Group, to ultimately reduce the risk and burden of cancer. As the second leg of this three-legged approach, the CP-CTNet will conduct early phase trials to assess the safety, tolerability, and cancer preventive potential of agents and interventions of varying classes identified by the first leg, i.e. the DCP's Cancer Preclinical Drug Development Program (PREVENT) support of preclinical/toxicology studies, many of which target molecules or processes known to be important during carcinogenesis. The CP- CTNet Sites will perform these early phase trials supported by the DCP and the CP-CTNet Data Management, Auditing, and Coordinating Center (DMACC). These trials include phase 0 (micro-dosing), phase I (dose- finding), and phase II (preliminary efficacy) clinical trials. To support these early phase trials, which will be conducted by the CP-CTNet sites alone or as cross-Network trials, the CP-CTNet DMACC will coordinate trans-Network activities and provide expertise and resources in 1) centralized data management and reporting, 2) clinical trials auditing, and 3) administrative and logistical coordination, including expertise in clinical trials methodology and biostatistics, across CP-CTNet. In addition, the CP-CTNet DMACC will provide an advisory role in early phase caner prevention trial development for all CP-CTNet trials and the primary statistical role for cross-Network trials.